Integrated Transcriptomic Analysis Reveals Conserved Inflammatory Transcriptional Signatures Across Bovine Mastitis and Endometritis: Shared Pathways and In Silico Candidate Agents

Mastitis and endometritis are prevalent infectious diseases in periparturient dairy cows, yet the shared transcriptional programs of the two conditions remain poorly defined. This study aimed to identify conserved inflammatory signatures and their upstream regulators and to explore candidate modulatory agents in silico. Using two public bovine transcriptomic datasets (GSE75379, GSE125964), we screened directionally concordant differentially expressed genes and performed integrated bioinformatic analyses, including functional enrichment, cell-type signatures (ssGSEA), WGCNA module preservation, cis-eQTL validation and regularized machine learning. Key findings were validated in two independent datasets, and candidate agents were screened using DGIdb 5.0 and HERB 2.0. We identified 383 concordantly upregulated and 61 concordantly downregulated genes, with NF-κB-mediated signaling as the key conserved pathway. The neutrophil signature was the only immune signature consistently enriched in both datasets. ISG15, SYK, and SELL formed a conserved 3-gene core signature with 100% directional concordance across two independent validation cohorts. In silico screening identified the SYK inhibitor fostamatinib and four traditional Chinese medicines as candidate modulators. In conclusion, the NF-κB inflammatory axis and the ISG15-SYK-SELL module form a conserved cross-tissue signature of bacterial mucosal inflammation, offering candidate targets and exploratory reference for the concurrent management of mastitis and endometritis.