Transcriptomic and proteomic profiling of early blood responses reveals pathways associated with distinct clinical outcomes following H7N1 high pathogenicity avian influenza virus infection in chickens.

High pathogenicity avian influenza (HPAI) poses a significant threat to poultry. Some chickens show resilience to HPAI, but the mechanisms involved are poorly understood. In this study, we aimed to identify the biological mechanisms associated with resilience to HPAIV infection in chickens. Chickens were inoculated with H7N1 HPAIV and classified as susceptible or resilient based on clinical signs, mortality, histopathological lesions, AIV antigen detection in tissues, and viral shedding. Blood transcriptomic analysis revealed that genes from resilient chickens are involved in the integrin-mediated signaling pathway (ITGA5, ITGA6, ITGB1), as well as in adaptive (BTK, TEC) and innate (TRIM13, LCK, TICAM1) immune pathways. Plasma proteomic profiling revealed that ARF4, EIF4A2, and HNRNPAB (proteins involved in fundamental cellular processes) were less abundant in resilient chickens compared to both controls and susceptible birds. Our results suggest that early modulation of these pathways is associated with resilience to HPAIV and likely reflects early viral control or reduced systemic dissemination rather than the absence of infection.