Early nasal and lung transcriptomic profiles reveal pathways associated with divergent clinical outcomes following H7N1 high pathogenicity avian influenza virus infection.

High pathogenicity avian influenza (HPAI) devastates the poultry industry worldwide due to its rapid spread, severe pathology, and high mortality in chickens. Why some infected birds survive while others die remains poorly understood. Here, we tracked early host transcriptomic responses (8-72 hours post-inoculation [hpi]) in the nasal turbinates and lungs of chickens infected with H7N1 HPAI virus. Chickens were classified as resilient or susceptible based on clinical signs, histopathological lesions, viral antigen detection, and viral shedding. Resilient chickens showed a distinct early transcriptional profile characterized by differential expression of genes related to MAPK signaling (CAV1), cell adhesion (ITGB1, PARVA), immune response (RELA), and antiviral response pathways (BID, CASP1, RAB2B). Critically, transcriptomic profiles of resilient birds differed markedly not only from susceptible birds but also from controls, consistent with viral exposure and an active host response. Our results suggest that the nasal mucosa is an important site in which early host responses are associated with divergent disease outcomes following HPAI viral infection.