The recently discovered influenza D virus (IDV) of the Orthomyxoviridae family has been detected in swine and ruminants with a worldwide distribution. Cattle are considered to be the primary host and reservoir and previous studies suggested a tropism of IDV for the upper respiratory tract and a putative role in the Bovine Respiratory Disease complex. This study aimed to characterize the pathogenicity of IDV in naive calves, as well as the ability of this virus to transmit by air. Eight naive calves were infected by aerosol with a recent French isolate, D/bovine/France/5920/2014. Results show that IDV replicates not only in the upper but also the lower respiratory tracts (LRT), inducing moderate bronchopneumonia with restricted lesions of interstitial pneumonia. Inoculation was followed by IDV-specific IgG1 production as early as 10 days post challenge, and likely both Th1 and Th2 responses. Study of the innate immune response in the LRT of IDV infected calves indicated the overexpression of pathogen recognition receptors and of chemokines CCL2, CCL3 and CCL4, but without overexpression of genes involved in the type I interferon pathway. Finally, virological examination of three aerosol-sentinel animals, housed 3 meters apart from inoculated calves, and IDV detection in air samples collected in different areas showed that IDV can be airborne transmitted and infect na?ve contact calves on short distances. This study suggests that IDV is a respiratory virus with moderate pathogenicity and probably a high level of transmission. It consequently can be considered as predisposing or co-factor of respiratory disease.IMPORTANCE Influenza D virus (IDV), a new Genus of the Orthomyxoviridae family, has a broad geographical distribution and can infect several animal species. Cattle are so far considered as the primary host for IDV, but the pathogenicity and the prevalence of this virus is still unclear. We demonstrated that under experimental conditions (in a controlled environment and in the absence of co-infecting pathogens), IDV is able to cause mild to moderate disease and targets both the upper and lower respiratory tracts. The virus can transmit by direct as well as aerosol contacts. While this study evidenced overexpression of pathogen recognition receptors and chemokines in the lower respiratory tract, IDV-specific IgG1 production as early as 10 days post challenge, and likely both Th1 and Th2 responses, further studies are warranted to better understand the immune responses triggered by IDV and its role as part of the Bovine Respiratory Disease complex.