When piglets are infected by virulent and avirulent strains of swine acute diarrhea syndrome coronavirus (SADS−CoV), there are obvious differences in their clinical symptoms; however, the specific mechanisms of pathogenicity and the immune regulation of highly pathogenic and low pathogenic strains are unknown. We collected intestinal tissues from SADS−CoV−infected piglets, performed a whole transcriptome sequencing analysis, including mRNA, miRNA, lncRNA, cicrRNA, and TUCP, and performed functional and correlation analyses of differentially expressed RNAs. Our results showed that the differentially expressed RNAs in group A versus group B (AvsB), group A versus group C (AvsC), and group B versus group C (BvsC) were relevant to immune and disease−related signaling pathways that participate in the organisms’ viral infection and immune regulation. Furthermore, data obtained from the HAllA analysis suggested that there was a strong correlation between the differentially expressed RNAs. Specifically, LNC_011487 in the P set was significantly negatively correlated with ssc−miR−215, and LNC_011487 was positively correlated with PI3. Moreover, we also constructed a differentially expressed RNA association network map. This study provides a valuable resource for studying the SADS−CoV transcriptome and pathogenic mechanism from the perspective of RNA to understand the differences in and consistency of the interaction between virulent and attenuated SADS−CoV strains and hosts.