Vampire bat interferon lambda 3 (IFN-λ3), also known as interleukin-28B (IL-28B), is a member of the type III interferon family (IFN-λ1/IL-29, IFN-λ2/IL-28A, IFN-λ3/IL-28B, and IFN-λ4) and functions as a critical antiviral cytokine that signals through the heterodimeric IFNLR1 (IL-28Rα)/IL-10R2 receptor complex, activating JAK/STAT pathways and inducing interferon-stimulated genes (ISGs) that restrict viral replication at epithelial surfaces. In vampire bats (Desmodus rotundus), recognized reservoirs for zoonotic viruses including rabies virus and other RNA viruses, IFN-λ3 is expected to play a central role in mucosal antiviral defense within the respiratory and gastrointestinal tracts while limiting excessive systemic inflammation. Because type III interferons primarily act on epithelial cells and generate a more localized antiviral response compared to type I interferons, IFN-λ3 may contribute to bats’ notable ability to tolerate viral infections without overt pathology. Characterizing vampire bat IFN-λ3 (IL-28B) provides important insight into mechanisms of viral control, immune modulation, and host–pathogen equilibrium, informing both wildlife disease management and broader research into antiviral immunity and zoonotic spillover risk.