The molecular mechanisms and hub genes identified for disease resistance in ducks against highly pathogenic avian influenza virus (HPAIV) infection show substantial variations between studies. This is mainly due to the limitations of small sample sizes owing to the huge cost of experimental infection and multiple other factors leading to the large variability of results. A metaanalysis can increase the statistical power for reliability and generalizability of previous studies to obtain more accurate results. Hence, this approach was used for identifying the molecular pathways and major hub genes responsible for disease resistance in ducks infected with HPAIVs. Meta-analysis using publicly available lung RNA seq datasets of ducks infected with HPAIVs, identified 339 differentially expressed genes (DEGs) (p-value cut-off ≤ 0.05); out of these, 214 genes were upregulated and 125 genes were downregulated. Network analysis of the DEGs suggests that infected ducks initiate a lower cytokine/chemokine response in comparison with control through the expression of anti-inflammatory effect genes (STATs, SOCSs and IL10) and a persistent antiviral immune gene expression through activation of RIG-I/MAVS/IFNAR1-dependent pathways in the lung. Further, genes such as STAT3, MYC, STAT1, MAPK11, RIPK1, SOCS3, SOCS1, and MYD88 were identified as the major regulators or hub genes responsible for disease pathogenesis in ducks. In conclusion, the powerful statistical meta-analysis approach led us to reveal molecular pathways and hub genes involved in the disease resistance mechanism in ducks infected with HPAIVs.

Highlights

• Duck initiates a lower cytokine response through expression of STATs, SOCSs and IL10.
• Persistent antiviral gene expression by activation of RIG-I/MAVS/IFNAR1 pathways.
• The STATs, SOCSs and MYD88 genes were main regulator genes for disease pathogenesis.