Contagious bovine pleuropneumonia (CBPP), caused by Mycoplasma mycoides subsp. mycoides (Mmm) , is a severe respiratory disease of cattle responsible for major economic losses in sub-Saharan Africa. Disease control relies mainly on the use of empirically attenu- ated vaccines that provide limited protection. Thus, understanding the virulence mechanisms used by Mmm as well as the role of the host immune system in disease development, persis- tence, and control is a prerequisite for the development of new, rationally designed control strategies. The aim of this study was to assess the use of whole blood transcriptome analysis to study cattle- Mmm interactions, starting by the characterization of the bovine response to Mmm infection during the acute form of the disease. For that purpose, we compared the tran- scriptome profile of whole blood from six cattle, before challenge by contact with Mmm - infected animals and at the appearance of first clinical signs, using a bovine microarray. Func- tional analysis revealed that 680 annotated genes were differentially expressed, with an over- whelming majority of down-regulated genes characterizing an immunosuppression. The main bio-functions affected were “ organismal survival ” , “ cellular development , morphology and functions ” and “ cell-to cell signaling and interactions ” . These affected functions were consis- tent with the results of previous in vitro immunological studies. However, microarray and qPCR validation results did not highlight pro-inflammatory molecules (such as TNF a , TLR2, IL-12B and IL-6), whereas inflammation is one of the most characteristic traits of acute CBPP. This global gene expression pattern may be considered as the result, in blood, of the local pulmo- nary response and the systemic events occurring during acute CBPP. Nevertheless, to under- stand the immune events occurring during disease, detailed analyses on the different immune cell subpopulations, either in vivo , at the local site, or