Three-way, large-scale survey of the bovine upper-respiratory metatranscriptome underscores the complex etiology of bovine respiratory disease

Bovine respiratory disease (BRD) is a major burden to the cattle industry. Its complex etiology involves viruses, bacteria, and host stressors, all of which contribute to disease development. In this study, we use publicly available metatranscriptome data from world-wide datasets to investigate how the bovine nasal virome, respiratory microbiome, and host transcriptome are associated with bovine respiratory disease. Our goal is to detect consistent signatures underlying bovine respiratory disease using a large sample of publicly available datasets. We detected 13 BRD-associated virus species in the publicly available samples. Eleven of them were found in samples of at least two continents, and 12 were found in both healthy and diseased animals. Viral diversity and abundance differed significantly based on geographic location, and certain viral pairs co-occur non-randomly. Interestingly, viral abundance was higher in healthy animals relative to diseased animals in two locations. Investigation of the bovine respiratory microbiome revealed differences in alpha diversity and beta diversity when considering sampling location and disease state. Of the notable bacterial genera associated with BRD, Mycoplasmopsis , Pasteurella , and Histophilus species were more abundant in animals with respiratory disease, while Moraxella was more abundant in healthy animals. Investigation of the host transcriptome revealed that animals with respiratory disease have coordinated changes in expression of genes involved in immunity and antiviral response in the respiratory tract, and some of these changes in the respiratory transcriptome are associated with changes in the abundance of pathogenic viruses and bacteria. Signatures underlying bovine respiratory disease can be detected across heterogeneous, publicly available datasets. Our study underscores the complex nature of bovine respiratory disease and highlights the need for more comprehensive techniques to study its host-microbe dynamics.