More than 4000 DEGs were identified using transcriptomics data to determine the severe effects of M. bovis spongiformis infection on calf tracheal tissues at the molecular level and enriched several important metabolic pathways associated with pathogen-infected calf tracheitis, mainly including the IL-17 signaling pathway, the Toll-like receptor signaling pathway, and the PI3K-Akt signaling pathway, which are associated with inflammatory injury. Here, AKT1 is linked to tracheitis.