Queues and transport mechanisms in Mule allow messages to be load balanced across multiple runtime nodes. There are three basic transport types - socket-based, listener-based, and resource-based. Resource-based transports like files require an explicit locking strategy to prevent duplicate processing, so it is best to immediately write messages to VM queues which allow other nodes to participate. Ensuring all cluster nodes are on the same LAN minimizes network interruptions and duplicates, though clustering across datacenters is possible but not recommended. Load balancers can distribute TCP requests to clustered instances for high availability.