Microorganisms of the genus Eperythrozoon are a zoonotic chronic infectious disease with wide distribution. We found that raccoons infected with Eperythrozoon showed obvious stunting, which seriously affected the economic benefits of raccoon dogs. To investigate the pathogenesis of the raccoon dog, we used transcriptome and proteome sequencing to analyze the changes in mRNA, miRNA, and protein expression in raccoon dogs infected with Eperythrozoon and normal raccoons. The results showed that the expression levels of genes related to immunity, metabolism, and enzyme activity were significantly changed. Among these, ERLIN1, IGF1R, CREB3L1, TNS1, TENC1, and mTOR play key roles. Additionally, the miR-1268, miR-125b, miR-10-5p, and miR-10 as central miRNAs regulate the expression of these genes. Integrated transcriptomic and proteomic analyses revealed consistent trends in mRNA and protein changes in MYH9, FKBP1A, PRKCA, and CYP11B2. These results suggest that Eperythrozoon may contribute to the slow development of raccoons by affecting the expression of mRNAs and miRNAs, reducing their immunity and causing metabolic abnormalities.