The MoTrPAC Study Group conducted a comprehensive multi-omic analysis of the temporal response to endurance exercise training in male and female rats over eight weeks. The study profiled the transcriptome, proteome, metabolome, lipidome, phosphoproteome, acetylproteome, ubiquitylproteome, epigenome, and immunome across 19 tissues, including whole blood, plasma, and 18 solid tissues. The data compendium includes 9,466 assays across 25 molecular platforms and four training time points, revealing thousands of shared and tissue-specific molecular changes, with sex differences observed in multiple tissues. The study identified extensive biological insights into the adaptive responses to endurance training, including widespread regulation of immune, metabolic, stress response, and mitochondrial pathways. Many of these changes are relevant to human health, such as non-alcoholic fatty liver disease, inflammatory bowel disease, cardiovascular health, and tissue injury and recovery. The data and analyses are publicly available at https://motrpac-data.org/. The study highlights the complex and dynamic molecular adaptations to endurance training across multiple tissues and omics. It shows that training induces significant changes in gene expression, protein abundance, post-translational modifications, and metabolite levels, with sex-specific responses observed in various tissues. For example, the adrenal gland showed opposite responses between males and females, while the liver exhibited substantial regulation of chromatin accessibility and metabolic pathways. The study also identified key pathways involved in immune responses, mitochondrial function, and lipid metabolism, which are relevant to human diseases such as type 2 diabetes, cardiovascular disease, obesity, and kidney disease. The research underscores the importance of multi-omic data in understanding the molecular mechanisms underlying the beneficial effects of exercise. It provides a valuable resource for studying the molecular changes associated with endurance training and offers insights into the potential therapeutic applications of exercise in improving health and managing disease. The MoTrPAC data resource is publicly accessible and includes tools for data exploration, analysis, and visualization, facilitating further research into the molecular basis of exercise-induced adaptations.The MoTrPAC Study Group conducted a comprehensive multi-omic analysis of the temporal response to endurance exercise training in male and female rats over eight weeks. The study profiled the transcriptome, proteome, metabolome, lipidome, phosphoproteome, acetylproteome, ubiquitylproteome, epigenome, and immunome across 19 tissues, including whole blood, plasma, and 18 solid tissues. The data compendium includes 9,466 assays across 25 molecular platforms and four training time points, revealing thousands of shared and tissue-specific molecular changes, with sex differences observed in multiple tissues. The study identified extensive biological insights into the adaptive responses to endurance training, including widespread regulation of immune, metabolic, stress response, and mitochondrial pathways. Many of these changes are relevant to human health, such as non-alcoholic fatty liver disease, inflammatory bowel disease, cardiovascular health, and tissue injury and recovery. The data and analyses are publicly available at https://motrpac-data.org/. The study highlights the complex and dynamic molecular adaptations to endurance training across multiple tissues and omics. It shows that training induces significant changes in gene expression, protein abundance, post-translational modifications, and metabolite levels, with sex-specific responses observed in various tissues. For example, the adrenal gland showed opposite responses between males and females, while the liver exhibited substantial regulation of chromatin accessibility and metabolic pathways. The study also identified key pathways involved in immune responses, mitochondrial function, and lipid metabolism, which are relevant to human diseases such as type 2 diabetes, cardiovascular disease, obesity, and kidney disease. The research underscores the importance of multi-omic data in understanding the molecular mechanisms underlying the beneficial effects of exercise. It provides a valuable resource for studying the molecular changes associated with endurance training and offers insights into the potential therapeutic applications of exercise in improving health and managing disease. The MoTrPAC data resource is publicly accessible and includes tools for data exploration, analysis, and visualization, facilitating further research into the molecular basis of exercise-induced adaptations.