There is a consensus that indigenous pigs in China are more resistant than modern commercial pigs in terms of disease resistance. Generally, the immune response is an important part of anti-disease capability; however, the related mechanism in pigs is largely puzzling. Here, the public transcriptome data of peripheral blood mononuclear cells (PBMCs) from Dapulian (Chinese local breed) and Landrace (Commercial breed) pigs after stimulation with polyinosinic-polycytidylic acid (poly I:C, a conventional reagent used for simulation of the viral infection) were reanalyzed, and the immune response mechanism in different pig breeds was investigated from a transcriptomic perspective. Of note, through comparative analyses of Dapulian and Landrace pigs, the candidate genes involved in swine broad-spectrum resistance were identified, such as , and . In addition, after differential gene expression, target gene identification and functional enrichment analyses, a potential regulatory network of miRNA genes associated with immune response was obtained in Dapulian pigs, including five miRNAs and 12 genes (such as ssc-miR-181a, ssc-miR-486, and ). This work provides new insights into the immune response regulation of antiviral responses in indigenous and modern commercial pigs.