Obesity-associated meta-inflammation alters influenza A antiviral responses in Göttingen minipigs.

Obesity is a well-recognized risk factor for increased severity following influenza A virus (IAV) infection, likely by promoting meta-inflammation and immune dysregulation, but its effects on antiviral and inflammatory responses remain poorly understood. Using a Göttingen minipig model of diet-induced obesity, we compared antiviral and inflammatory responses before and after IAV infection. Respiratory tract transcriptomics and histopathology revealed no clear obesity-associated immune or inflammatory changes in uninfected minipigs. In contrast, obese pigs showed reduced viral clearance in nasal mucosal tissue accompanied by altered antiviral gene expression pattern 4 days post-infection. Furthermore, cellular infiltration of the respiratory tract was observed in obese pigs after infection. Finally, C-reactive protein concentrations increased significantly in obese pigs, indicating enhanced systemic inflammation in response to respiratory infection. These findings demonstrate that diet-induced obesity in Göttingen minipigs is associated with altered antiviral and inflammatory responses following IAV infection and support the translational value of the obese minipig model.