3D genome of porcine alveolar macrophages: CD163 exon 7 deletion spares stability but unveils breed-associated architecture

Porcine reproductive and respiratory syndrome virus (PRRSV) causes substantial economic losses to the global swine industry. Targeted deletion of CD163 exon 7 confers PRRSV resistance, but its broader genomic consequences remain incompletely understood. Here, we integrated chromosome conformation capture (Hi-C) and RNA sequencing to characterize chromatin organization and gene expression in unstimulated porcine alveolar macrophages (PAMs) from CD163-edited Landrace and Duroc pigs. We detected no significant editing-associated changes in CD163 expression, global 3D genome organization, chromatin architecture at the CD163 locus, or transcriptomic profiles within either breed. Comparative analyses revealed breed-associated differences in gene expression and chromatin interactions between edited Landrace and Duroc pigs. Integrative analyses prioritized three immune-related candidate genes— ICAM1 , IRF1 , and TNFRSF17 —based on associations involving SNP variation, chromatin interactions, and gene expression differences. Collectively, this study provides a multi-omics resource for investigating the molecular consequences of CD163 exon 7 deletion and breed-associated immune variation in pigs.