Comparative Transcriptomics Reveals Breed‑Specific Ferroptosis and Ribosomal Signatures Associated with Riemerella anatipestifer Resistance in Ducks

Riemerella anatipestifer ( RA ) is a major pathogen causing substantial economic losses in the duck industry. Unravelling the mechanisms governing differential susceptibility and resistance to RA infection is essential for developing effective disease control strategies. Herein, we compared transcriptomic responses to RA challenge between two genetically distinct duck breeds: commercial White Kaiya (WK) and indigenous Ji’an Red-feathered (JR) ducks. Each breed contained resistant (R) and susceptible (S) individuals, designated as R-JR, S-JR, R-WK, and S-WK groups. GO and KEGG enrichment analyses revealed significant ferroptosis pathway enrichment in the S-JR, R-WK, and S-WK groups ( P < 0.05), whereas no significant enrichment observed in R-JR ducks ( P = 0.6936). RT‑qPCR confirmed that S-JR ducks exhibited up-regulated pro-ferroptotic genes ( TF, TFRC, PTGS2, SLC7A11 ) and down-regulated iron exporter SLC40A1 , whereas these genes remained at basal levels in R-JR ducks. In WK ducks, SLC40A1 was down-regulated in both R and S individuals, and pro-ferroptotic genes showed stronger upregulation in S-WK ducks. Furthermore, ribosome and B-cell receptor signaling were uniquely enriched in R-JR ducks. Fourteen pathways, including ER protein processing, proteasome, oxidative phosphorylation, cell cycle, and multiple biosynthetic/metabolic pathways, were universally activated across all groups, while five pathways (MAPK, ABC transporters, PI signaling, Notch, Hedgehog) were downregulated. We further validated four susceptibility candidate genes ( SELE, ADAMTS4, IL8 , and IL6 ) upregulated in susceptible ducks from both breeds. TUNEL staining revealed increased TUNEL-positive signals in susceptible groups, whereas resistant ducks maintained signal levels comparable to controls. Overall, this study provides novel molecular evidence for breed-specific RA resistance and highlights ferroptosis, ribosomal, and cell death pathways as potential targets for selective breeding and therapeutic development in waterfowl.