The study reports the detection and genomic characterization of highly pathogenic avian influenza (HPAI) A (H5N1) clade 2.3.4.4b viruses in dairy cattle, domestic cats, and wild birds in Texas. These viruses, which had not previously been reported in domestic cattle, caused a sudden drop in milk production in affected dairy cows. The viruses share nearly identical genome sequences, forming a new genotype B3.13 within the 2.3.4.4b clade. They underwent two reassortment events since 2023 and exhibit critical mutations in the HA, M1, and NS genes but lack key mutations in PB2 and PB1 genes that enhance virulence or adaptation to mammals. The PB2 E627K mutation in a human case highlights the potential for rapid evolution post-infection. The study emphasizes the need for continued surveillance to monitor public health threats, particularly the risk of zoonotic transmission through unpasteurized milk. The outbreak's occurrence in March, coinciding with the spring migration season, suggests that wild birds may have played a significant role in the virus's dissemination. The presence of the same strain in various wild bird species and the detection in multiple states further support this hypothesis. The study also discusses the mutation adaptations, particularly those linked to human receptor binding affinity and increased virulence, which raise concerns about cross-species transmission to humans and other mammalian species.The study reports the detection and genomic characterization of highly pathogenic avian influenza (HPAI) A (H5N1) clade 2.3.4.4b viruses in dairy cattle, domestic cats, and wild birds in Texas. These viruses, which had not previously been reported in domestic cattle, caused a sudden drop in milk production in affected dairy cows. The viruses share nearly identical genome sequences, forming a new genotype B3.13 within the 2.3.4.4b clade. They underwent two reassortment events since 2023 and exhibit critical mutations in the HA, M1, and NS genes but lack key mutations in PB2 and PB1 genes that enhance virulence or adaptation to mammals. The PB2 E627K mutation in a human case highlights the potential for rapid evolution post-infection. The study emphasizes the need for continued surveillance to monitor public health threats, particularly the risk of zoonotic transmission through unpasteurized milk. The outbreak's occurrence in March, coinciding with the spring migration season, suggests that wild birds may have played a significant role in the virus's dissemination. The presence of the same strain in various wild bird species and the detection in multiple states further support this hypothesis. The study also discusses the mutation adaptations, particularly those linked to human receptor binding affinity and increased virulence, which raise concerns about cross-species transmission to humans and other mammalian species.