Abstract
Porcine reproductive and respiratory syndrome virus (PRRSV) is a major threat to the global swine industry. Long non-coding RNAs (lncRNAs) are emerging as crucial regulators of antiviral immunity, but their roles in porcine alveolar macrophages (PAMs)-the primary target of PRRSV-remain poorly characterized. This study presents a genome-wide analysis of lncRNA expression in PAMs stimulated with a PRRS modified live virus (MLV) vaccine and two type I interferons, IFN-α1 and IFN-ω5. Whole-transcriptome sequencing identified over 2000 differentially expressed lncRNAs, with IFN-ω5 inducing the most extensive transcriptional reprogramming. Weighted gene co-expression network analysis (WGCNA) revealed interferon-specific lncRNA-mRNA modules, and functional enrichment showed these lncRNAs are involved in key immune and metabolic pathways, including chemokine signaling, MAPK, and mTOR. Our findings establish a comprehensive landscape of lncRNA regulation in PAMs, highlighting their role in fine-tuning the antiviral responses and suggesting novel targets for interferon-based antiviral interventions against PRRSV.